Lymphocytes from lymph nodes obtained at mastectomy from breast cancer patients have been fused with murine non-immunoglobulin (Ig) secreting myeloma cells to obtain human-mouse hybridoma cultures that synthesize human monoclonal antibodies. Several assays were used to demonstrate that the Ig's produced by the interspecies hybridomas were indeed human and not murine. The immunologic reactivities of the human Ig's were assayed with the immunoperoxidase method using tissue sections of the primary tumor from the patient whose lymphocytes were used for fusion, as well as using tissue sections from other primary tumors. One human IgM monoclonal was used to discriminate between mammary carcinoma cells (from 55 of 59 patients) and normal mammary epithelial cells, stroma, or lymphocytes of the same breast. This same antibody reacted with selected non-breast carcinomas and metastatic mammary carcinoma cells in lymph nodes and at distal sites. Experiments are in progress to develop nonhuman primate monoclonal antibodies using lymphocytes from old world monkeys and chimpanzees immunized with membrane enriched extracts of human mammary tumors.